• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1649-1654
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• 2014

Background: Clinically significant portal hypertension (PHT) is considered as a contraindication for hepatectomy according to the guidelines of the European Association for Study of Liver and the American Association for Study of Liver Diseases. However, this issue remains controversial. Here we performed a metaanalysis to evaluate the impact of PHT on the results of hepatectomy for hepatocellular carcinoma (HCC). Methods: Cohort studies evaluating the impact of clinically significant PHT, defined as oesophageal varices and/or splenomegaly associated with thrombocytopenia, on the results of hepatectomy for HCC were identified using a predefined search strategy. Summary risk ratios (RRs) and 95% confidence intervals (95% CIs) for PHT and outcomes after hepatectomy for HCC were calculated. Results: Seven cohort studies which including 574 cases with PHT and 1,354 cases without PHT were considered eligible for inclusion. The meta-analysis showed that, in all patients, pooled RRs of post-operative liver failure, post-operative ascites, peri-operative blood transfusion, operative mortality, 3- and 5-year overall survival associated with PHT were 2.23 (95% CI: 1.48-3.34, P=0.0001), 1.77 (95% CI: 1.19-2.64, P=0.005), 1.23 (95% CI: 1.03-1.49, P=0.03), 2.58 (95% CI: 1.12-5.96, P=0.03), 0.82 (95% CI: 0.75-0.88, P<0.00001) and 0.76 (95% CI: 0.69-0.85, P<0.00001), respectively. In subgroup analysis, similar results were found in Child-Pugh class A patients. Conclusion: This meta-analysis suggests that presence of oesophageal varices and/or splenomegaly associated with thrombocytopenia is associated with higher rates of post-operative complications and poor long-term survival after hepatectomy for HCC.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.443-448
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• 1996

The effects of Taheebo on the diabetic-piegnant rats and their fetus was investigated. It has been reported that diabetic condition of the pregnant rats can affect the process of liver formation and damage the respiratory function in the fetus. Therefore we investigated the effects of Taheebo on the prevention of liver damage and respiratory failure in the fetus and those results were compared with that of dexamethasone (DXM). In pregnant rats, streptozotocin(STZ, 45 mg/kg, 0.01 M citrate buffer) was injected into the pregnant rats on the third day of pregnancy. Methanol extracts of Taheebo(500 mg/kg p.o.) was administered once daily during pregnancy. DXM (10 $\mu\textrm{g}$/g i.p.) was injected into the pregnant rats in 16th and 18th days of pregnancy. Body weights were measured and fetal number and abortion rate in pregnancy rats were determined. Lecithin/sphingomyelin ratio in amniotic fluid and malondialdehyde, glycogen, triglyceride, protein and cholesterol levels in the liver homogenate were determined. Also blood glucose level was analyzed. Body weights of maternal rats were increased in the all groups except the DXM group. Fetal number of the Taheebo treated group was similar to the control group, and a significant increase in the body weights of fetus was observed in the STZ treated group and the Taheebo treated group compared with the control group. Blood glucose of fetus produced hypoglycemia in the control group and hyperglycemia in the diabetic-pregnant rats. The protein and cholesterol levels in fetus liver were significantly increased in the DXM treated group compared with the control group. Triglyceride content was significantly increased in all groups compared with the control group. Liver malondialdehyde level of fetus in the STZ treated group was similar to the control group. Glycogen level was significantly increased in the all groups compared with the control group. Methanol extract of Taheebo showed hypoglycemic effect on the pregnant rats. However, we could not observe any hypoglycemic effect on the fetus. There's no difference between the control and Taheebo treated group in terms of the levels of triglyceride, cholesterol, protein and glycogen in the fetus liver. Further study to identify the effect of Taheebo on the fetus is under investigation.

• Molecules and Cells
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• 제38권10호
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• pp.843-850
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• 2015

The1hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

• Journal of Korean Medical Science
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• 제33권51호
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• pp.324.1-324.6
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• 2018

Oxysterol $7{\alpha}$-hydroxylase deficiency is a very rare liver disease categorized as inborn errors of bile acid synthesis, caused by CYP7B1 mutations. As it may cause rapid progression to end-stage liver disease even in early infancy, a high index of suspicion is required to prevent fatal outcomes. We describe the case of a 3-month-old boy with progressive cholestatic hepatitis and severe hepatic fibrosis. After excluding other etiologies for his early liver failure, we found that he had profuse urinary excretion of $3{\beta}$-monohydroxy-${\Delta}^5$-bile acid derivatives by gas chromatography/mass spectrometry analysis with dried urine spots on filter paper. He was confirmed to have a compound heterozygous mutation (p.Arg388Ter and p.Tyr469IlefsX5) of the CYP7B1 gene. After undergoing liver transplantation (LT) from his mother at 4 months of age, his deteriorated liver function completely normalized, and he had normal growth and development until the current follow-up at 33 months of age. We report the first Korean case of oxysterol $7{\alpha}$-hydroxylase deficiency in the youngest infant reported to undergo successful living donor LT to date.

• 대한간학회지
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• 제24권4호
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• pp.358-366
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• 2018

Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called "6-month rule." This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.

• 대한약침학회지
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• 제22권4호
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• pp.239-247
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• 2019

Objectives: Allium jesdianum (Aj) is a medicinal plant that has highlighted pharmacological features. In this study, the effects of Aj extract were examined on acetaminophen (APAP)-induced hepatic failure in rats. Methods: Methanolic fraction of hydro-alcoholic extract of Aj was obtained by silica gel column chromatography method. Animals were randomly divided into four groups each containing six rats and treated by gavage as follows: the first and second groups received normal saline, the third and fourth groups were received with 50 and 100 mg/kg of Aj extract, respectively. After two consecutive weeks, the groups 2-4 were given a single dose of APAP (2 g/kg). After 48 hours, blood and liver samples were collected for biochemical and histological examinations. Results: The findings of the study demonstrated that APAP caused a significant increase in ALT (P < 0.001), AST (P < 0.001), LDH (P < 0.001), ALP (P < 0.001) serum levels, hepatic lipid peroxidation (LPO; P < 0.001) and nitric oxide (NO; P < 0.001). In this regard, APAP led to the depletion of the total antioxidant capacity (TAC; P < 0.001), glutathione and total thiol groups (TTGs; P < 0.001), and structural change in the liver. In the Aj extract groups, a considerable improvement was found in the hepatic function alongside the histopathologic changes. Conclusion: This investigation indicated that the influential effects of Aj extract in APAP-induced hepatic failure might depend on its effect on improving oxidant/antioxidant balance in hepatic tissue.

• 대한수의학회지
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• 제30권4호
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• pp.441-446
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• 1990

Encephalomyocarditis virus infection in pigs, characterized by severe reproductive failure in sows and sudden death in less than 7 day-old-piglets, a period of several months from October to December of 1989, in Korea was occurred. The most outstanding gross lesions at necropsy were found in the heart which were consisted of pale, yellow brown necrotic foci of varying size in myocardium. In some cases, pulmonary edema and liver congestion were observed. Histopathology of the heart revealed the interstitial myocarditis, endocarditis and epicarditis with lymphocytic, plasmacytic and macrophage cell infiltration and, in some cases, calcification of the necrotic myocardial muscle fibers. In some cases of brain, the perivascular cuffing and glial nodules were observed. In the liver and the lacrimal gland varying degrees of multifocal necrosis were seen. The virus was isolated from the heart and the brain in a stillborn piglet and a mummified fetus. This outbreak represents the first case of encephalomyocarditis virus infection of pigs in Korea.

• 대한임상독성학회지
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• 제12권1호
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• pp.31-34
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• 2014

We report on a patient who developed acute hepatic failure despite intravenous N-acetyl cysteine therapy who was treated with the Molecular Adsorbents Recirculating System (MARS). She presented 20 hours after the ingestion of 13 g of acetaminophen. The MARS is based on albumin dialysis principle which can be applied for patients with acute poisoning from drugs that have high protein-binding capacity because of its ability to selectively remove from circulation protein-bound toxins. The clinical toxicologist should be consider this technology when treating patients with hepatic failure following acetaminophen poisoning.

• 대한의생명과학회지
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• 제19권4호
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• pp.310-314
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• 2013

CYP2E1 in the liver has been studied intensively because it is involved in the metabolic activation of xenobiotics. It is inducible by alcohol, so it has been suspected as the cause of cancer in the stomach and lung. The possible role of CYP2E1 has been suggested strongly as causing tissue damage in mice with renal failure. It was also suspected that 5'-flanking region of CYP2E1 gene might be involved with renal failure. So, we investigated polymorphism of restriction enzyme sites within CYP2E1 gene using the PCR-RFLP analysis. PstI and RsaI sites were located at 5'-flanking region and DraI site was located at intron 6. All three types (W/W, W/S, S/S) were observed for these enzymes although each incidence was somewhat different depending the enzyme sites. W/W was prominent for PstI whereas W/S was markedly high for RsaI. Overall, polymorphic incidence in patients was somewhat higher than normal population. This research should facilitate further investigation of CYP2E1 at genetic level as the direct cause of tissue damage in various organs.

• Archives of Pharmacal Research
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• 제13권3호
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• pp.233-239
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• 1990

The efect of acute renal failure (ARF) on the pharmacokinetics o sulfobromophthalein (BSP) was investigated in order to elucidate if renal failure modifies the hepatic metabolism of drugs. ARF was induced by intravenous (iv) injection of uranyl nitrate (UN) to rats (5 mg/kg) five days before the experiment. Area under the plasma concentration-time curve (AUC)of BSP after portal vein (pv) injection increased by 2-fold and total body clearance ($CL_1$) decreased one half (p <0.01) in UN-induced ARF (UN-ARF) rate compared to the control rats. But the plasma disappearance of BSP after iv injection did not differ significantly between control and UN-ARF rats. Since BSP is excreted via the liver, $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represents a decrease in hepatic intrinsic clearance ($CL_{int}$) for BSP since plasma free fraction ($f_p$) of BSP was not affected by UN-ARF. The content of hepatic cytoplasmic Y-protein, which catalyzes BSP-glutathione conjugation and limits the trasfer of BSP from blood to bile, increased significantly (p < 0.01), however its binding activity (BA) for BSP was decreased significantly (p <0.01) by UN-ARF. The decrease in $CL_{int}$might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP.